Glucagon Responses During Oral- and iv Glucose in Patients With Type 1 Diabetes

University Hospital, Gentofte, Copenhagen20 enrolled

Overview

In order to evaluate the potential role of the gastrointestinal (GI) tract in the postprandial hyperglucagonemia, which characterizes type 1 diabetes mellitus (T1DM) (as well as type 2 diabetes mellitus (T2DM)), we wish to investigate the secretion of glucagon in patients with T1DM without residual beta-cell function during 50-g oral glucose tolerance test (OGTT) and during isoglycemic iv glucose infusion. By evaluating C-peptide negative patients with T1DM we aim to describe the glucagon response to glucose (+/-stimulation of the GI tract) independently of the potentially very important regulation of glucagon secretion by endogenous insulin secretion. A more detailed understanding of the inappropriate glucagon secretion in T1DM is highly needed in order to establish new intervention strategies in the future treatment of the growing numbers of T1DM patients.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Hyperglucagonemia Hyperglycemia Diabetes Mellitus

Interventions

Isoglycemic iv glucose infusionOTHER

The plasma glucose curve obtained during a 50 g-OGTT (performed on a separate day) is copied using an adjustable iv glucose infusion (20% w/v) performed following a 10-h fast including liquids and medication (if any). The iv catheter is inserted into a peripheral vein in the hand/forearm.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Caucasian over 18 years with T1DM (diagnosed according to WHO's criteria) treated with long-acting insulin * No residual beta-cell function (arginine test without increment in plasma C-peptide - see below) * BMI \<30 kg/m2 * Normal haemoglobin * Informed consent Exclusion Criteria: * Residual beta-cell function (increment in plasma C-peptide during arginine test - see below) * Known liver disease or affected liver enzymes (ALAT/ASAT \> 2 x upper normal limit) * Diabetic nephropathy (se-creatinin \> 130 µM and/or albuminuria) * Proliferative diabetic retinopathy (anamnestic) * Treatment with medication that cannot be discontinued for 14 hours

Outcomes

Primary Outcomes

Glucagon responses (as assessed by area under curve (AUC)) during 50-g oral glucose tolerance test (OGTT) and isoglycemic iv glucose infusion, respectively.

Time frame: months

Secondary Outcomes

Responses of glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) as assessed by AUC during 50-g OGTT and isoglycemic iv glucose infusion, respectively.